The goal of the proposed work is to develop a simple, robust, and cost-efficient circulating tumor cell (CTC) isolation system based on an innovative BUBLES (BUoyancy enaBLEd Separation) technology for point-of- care applications. The feasibility of this technology has been recently established by using targeted microbubbles to isolate CTCs from blood samples in both research and clinical settings. The Phase I goal has been achieved through the development and test of a microbubble separator/harvester prototype device to capture rare tumor cells in more than 7 ml of blood samples. Under Phase II funding, we propose to complete the engineering work by creating an inexpensive and user-friendly automated CTC isolation system based on the core BUBLES technology, to validate the system with a study using human blood samples, and to broaden the use of isolated CTCs for more research and clinical applications in addition to the simple CTC enumeration. In contrast to many other CTC isolation systems that generally require centralized laboratories to process samples, our product, which is much less complex to build and operate, targets the primary care and small laboratory settings. Compared to other competitors, we will have less cost but faster production and broader market size for commercialization.